1. Field of the Invention
This invention relates to novel organosilane derivatives of 7-aminocephalosporanic acid ("7ACA") and 7-amino-desacetoxycephalosporanic acid ("7ADCA"). More specifically, this invention relates to the use of these novel organosilane derivatives for the synthesis of .DELTA..sup.3 -cephalosporins. Additionally, this invention deals with a specified set of reaction conditions whereby .DELTA..sup.3 -cephalosporins are produced utilizing the above organosilane derivatives without the formation of the less desirable .DELTA..sup.2 -isomers.
2. Description of the Prior Art
The use of tri-organo substituted silane ("silyl") intermediates for the synthesis of cephalosporins from 7-ACA and 7-ADCA has been described in several patents and is well known in the prior art. However, the use of di-organo substituted silane ("silene") intermediates for the synthesis of cephalosporins has been described only fleetingly in the prior art.
For example, British Pat. No. 1,073,530 discloses the synthesis of cephalosporins by silylating "7ACA" with monohalosilanes, silazanes or silylamines followed by acylating the intermediate trialkyl silyl derivative of "7ACA". U.S. Pat. No. 3,671,449 discloses mono and di-silylated "7-ACA" and "7ADCA" and processes for their preparation with mono or bissilylamides, silylureas and silylurethanes as silylating agents. Additionally, this particular patent discusses various reasons why halosilanes should not be used as silylating agents.
Netherlands Pat. No. 6,401,841 deals with the use of dialkyldihalosilanes in preparing 6-aminopenicillanic acid intermediates. This patent also mentions the possibility that aminocephalosporanic acid can be used in this procedure.
Netherlands Pat. No. 7,105,259 discloses and claims the preparation of cephalosporins by reacting 7ACA and 7ADCA with a dialkoxyldihalosilane or an alkylene dioxydihalosilane, acylating the intermediate and hydrolyzing the resulting product. This patent is the only patent in the cephalosporin prior art which actually exemplifies silylation or silenation with a halosilane. However, there is no mention in the above prior art of the problem of isomerization of the double bond of .DELTA..sup.3 -cephalosporins and particularly esters of .DELTA..sup.3 -cephalosporins to the less active .DELTA..sup.2 -isomers by the action of bases such as triethylamine or pyridine. This problem is discussed in an article by J.D. Cocker, et. al. entitled Cephalosporanic Acids. Part IV 7-Acylamidoceph-2-em-4-carboxylic Acids appearing in the Journal of the Chemical Society 1966, 1142.